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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 7, 2015; 21(41): 11740-11747
Published online Nov 7, 2015. doi: 10.3748/wjg.v21.i41.11740
Neuroendocrine differentiation: The mysterious fellow of colorectal cancer
Britta Kleist, Micaela Poetsch
Britta Kleist, Department of Pathology, Southern Hospital Trust, 4604 Kristiansand, Norway
Micaela Poetsch, Institute of Legal Medicine, University Hospital Essen, 45122 Essen, Germany
Author contributions: Kleist B and Poetsch M analyzed the literature and wrote the manuscript.
Conflict-of-interest statement: The authors have no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Britta Kleist, MD, PhD, Department of Pathology, Southern Hospital Trust, Postbox 416, 4604 Kristiansand, Norway. britta.kleist@sshf.no
Telephone: +47-3807-3071 Fax: +47-3807-3076
Received: April 27, 2015
Peer-review started: April 30, 2015
First decision: June 23, 2015
Revised: July 7, 2015
Accepted: September 15, 2015
Article in press: September 15, 2015
Published online: November 7, 2015
Processing time: 190 Days and 12.8 Hours
Abstract

Neuroendocrine differentiation in sporadic colorectal cancer has been recognized since decades, but its clinical impact is still controversially discussed. Detailed parameter analyses hint at the possibility that probably not neuroendocrine differentiation itself, but its association with poor grade of tumor differentiation, lymph node metastases, distant metastases and other unfavorable features contribute to worse clinical outcome. However, other studies deny a relationship between neuroendocrine differentiation and prognosis of colorectal cancer. This review elucidates, whether new insights into the origin of neuroendocrine differentiation in the intestinal epithelium, its regulation by mTOR pathway components and its possible link to the intestinal stem cell compartment could determine a role of neuroendocrine cells as prognostic marker and putative therapeutic target in sporadic colorectal cancer.

Keywords: Neuroendocrine differentiation; Colorectal cancer; mTOR pathway; Neuroendocrine tumorigenesis; Targeted therapy

Core tip: Neuroendocrine differentiation in sporadic colorectal cancer has been recognized since decades. In contrast to the clinico-pathologically well-defined pure neuroendocrine tumors and mixed adenoneuroendocrine carcinomas of the colon and rectum, the clinical impact of focal neuroendocrine differentiation in colorectal carcinomas is still controversially discussed. Further insights into the regulation of neuroendocrine differentiation by mTOR pathway components and recent knowledge about a link of enteroendocrine cells to the intestinal stem cell compartment hint at a role of neuroendocrine cells as prognostic marker and putative therapeutic target in sporadic colorectal cancer.